Osteopontin is elevated in Parkinson’s disease and its absence leads to reduced neurodegeneration in the MPTP model

Maetzler, Walter; Berg, Daniela; Schalamberidze, Natalie; Melms, Arthur; Schott, Klaus; Mueller, Jakob C.; Liaw, Lucy; Gasser, Thomas; Nitsch, Cordula

doi:10.1016/j.nbd.2006.10.020

Cited by 108 publications

(100 citation statements)

References 44 publications

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“…At the cellular level, the protein has proadhesive, chemotactic and cytokine-like properties, and is involved in a number of physiologic and pathologic events including angiogenesis, apoptosis, inflammation, oxidative stress, remyelination, wound healing, bone remodeling, cell migration and tumorigenesis (Chakraborty et al 2006;El-Tanani et al 2006;Pagano and Haurani 2006). As some of these events lead to neurodegeneration (Maetzler et al 2007;Wung et al 2007) whereas others to neuroprotection (Meller et al 2005;Schroeter et al 2006), the overall outcome in sensorimotor neurons may have been neutralized in the null deletion.…”

Section: Discussionmentioning

confidence: 99%

Osteopontin is not Critical for Otoconia Formation or Balance Function

Zhao

Jones

Thoreson

et al. 2008

JARO

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Unlike the structural and mechanical role of bone crystals, the inertial mass of otoconia crystals provides a shearing force to stimulate the mechanoreceptors of the utricle and saccule (the gravity receptor organ) under the stimuli of linear motion. It is not clear whether otoconia, composed primarily of CaCO 3 and glycoproteins, go through similar calcification processes as bone. We have recently shown that otoconin-90 (Oc90) regulates the growth of otoconia crystals as osteopontin does bone crystals. Here, we analyzed the role of this non-collagenous bone matrix protein, osteopontin, in otoconia formation and balance function utilizing its knockout mice, whose inner ear phenotype has not been examined. Despite the presence of the protein in wild-type otoconia and vestibular hair cells, morphological, ultrastructural, and protein and calcium composition analyses of osteopontin null otoconia show that the protein is not needed for crystal formation, and no evidence of compensatory protein deposition is found. Employment of a wide spectrum of balance behavioral tests demonstrates that the protein is not critical for balance function either, which is confirmed by the normal function of the gravity receptor organ directly measured with linear vestibular-evoked potentials (VsEPs). When compared with findings on other otoconins, the data manifest a hierarchy of importance of proteins in crystallization and indicate mechanistic similarities and differences between bone and otoconia calcification.

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Section: Discussionmentioning

confidence: 99%

Osteopontin is not Critical for Otoconia Formation or Balance Function

Zhao

Jones

Thoreson

et al. 2008

JARO

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“…The pathogenesis of Parkinson's disease involves processes such as oxidative and nitrosative stress, apoptosis, mitochondrial dysfunction, and excitotoxicity, in all of which OPN may play a role. It was suggested that OPN is involved in Parkinson's-associated neurodegeneration because OPN is elevated in Parkinson's disease and its absence leads to reduced neurodegeneration in the MPTP model (Maetzler et al, 2007). …”

Section: Opn and Stressmentioning

confidence: 99%

“…Its expression is elevated in response to mechanical stress in bone and the vasculature Yoshitake et al, 1999;Denhardt and Noda, 1998). OPN levels are elevated in response to the oxidative stresses existing in tumors, after reperfusion injury, and in inflammatory diseases such as inflammatory bowel disease, chronic obstructive pulmonary disease, and Parkinson's disease (Maetzler et al, 2007;Da Silva et al, 2006;Heguy et al, 2007). Our finding that mice lacking OPN are protected from stress-induced lymphoid organ atrophy is intriguing because this implies that OPN also functions as a stress mediator.…”

Section: Opn Is Implicated In Immune and Inflammatory Responses For mentioning

confidence: 99%

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Osteopontin: Role in immune regulation and stress responses

Wang¹,

Denhardt²

2008

Cytokine & Growth Factor Reviews

603

558

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“…OPN expression is increased in response to various stressors, including physical and chemical stress (16,17). A connection between stress and immune function has been demonstrated in various experimental paradigms (18).…”

mentioning

confidence: 99%

Osteopontin regulates hindlimb-unloading-induced lymphoid organ atrophy and weight loss by modulating corticosteroid production

Wang¹,

Shi²,

Denhardt

2007

Proc. Natl. Acad. Sci. U.S.A.

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Osteopontin (OPN), a multifunctional secreted phosphoglycoprotein, plays diverse roles in bone biology, immune regulation, cell survival, inflammation, and cancer metastasis. Here we show its role in determining lymphocyte homeostasis and body mass in response to hindlimb unloading (HU), a model for evaluating effects of weightlessness on the musculoskeletal and other physiological systems. Using this stress model, we compared OPN ؊/؊ mice with OPN ؉/؉ mice subjected to HU for 3 days. Whereas OPN ؉/؉ mice suffered a marked reduction of body weight and significant spleen and thymus atrophy, OPN ؊/؊ mice exhibited minor weight loss and much less spleen and thymus atrophy. The HU-induced lymphoid organ atrophy was the result of dramatically diminished numbers, respectively, of T and B cells in the spleen and CD4 ؉ CD8 ؉ double-positive cells in the thymus of OPN ؉/؉ mice. Increased levels of corticosterone, which modulates lymphocyte activation responses and apoptosis during stress, were found only in OPN ؉/؉ mice. Apoptotic cell death was evident in the spleen and thymus of OPN ؉/؉ mice subjected to HU but not in OPN ؊/؊ mice. Importantly, lymphocytes from both OPN ؉/؉ and OPN ؊/؊ mice were equally sensitive to corticosteroid-induced apoptosis. These results reveal that OPN is required for enhanced corticosterone production, immune organ atrophy, and weight loss in mice subjected to HU. apoptosis ͉ immune ͉ stress ͉ lymphocytes ͉ space flight

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Osteopontin is elevated in Parkinson’s disease and its absence leads to reduced neurodegeneration in the MPTP model

Cited by 108 publications

References 44 publications

Osteopontin is not Critical for Otoconia Formation or Balance Function

Osteopontin is not Critical for Otoconia Formation or Balance Function

Osteopontin: Role in immune regulation and stress responses

Osteopontin regulates hindlimb-unloading-induced lymphoid organ atrophy and weight loss by modulating corticosteroid production

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